3.1. Chemistry
3.1.1. General
All the microwave-assisted reactions were carried out in a CEM Focused Microwave Synthesis System, Model Discover, working at the power required for refluxing under atmospheric conditions. Melting points were determined on a Buchi Melting Point B-545 apparatus and are uncorrected. Elemental analyses (C, H, N) were carried out on a Carlo Erba Model 1106 Elemental Analyzer and the results were within ±0.4% of the theoretical values. Merck silica gel 60 F
254 plates were used for analytical TLC; column chromatography was performed on Merck silica gel 60 (230–400 mesh), and Flash Chromatography (FC) on a Biotage SP
1 EXP.
1H-NMR spectra were recorded in CDCl
3 with TMS as internal standard or DMSO-
d6 on a Varian Gemini-300 spectrometer. Chemical shifts were expressed in δ (ppm) and coupling constants (
J) in hertz (Hz). All the exchangeable protons were confirmed by addition of D
2O. 3-Acetyl-4-methoxy-1
H-indole (
4) was synthesized following the previously reported procedure [
18]. Briefly, phosphoryl chloride (0.92 mL, 10 mmol) was added to ice cold dimethylacetamide (2.79 mL, 30 mmol) under stirring and cooling in ice. 4-Methoxy-1
H-indole 5 (147.18 mg, 1 mmol) was added and the reaction mixture was stirred at room temperature for 12 h, then poured over ice and basified with 4 N aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate and dried over Na
2SO
4. After removal of the solvent under reduced pressure, the residue was crystallized by treatment with diethyl ether and recrystallized from dichloromethane. mp 113–115 °C, yield 89%.
1H-NMR (δ) 2.70 (s, 3H, CH
3), 3.97 (s, 3H, OCH
3), 6.68–7.79 (m, 4H, ArH), 8.69 (br s, 1H, NH). Anal. Calcd for C
11H
11NO
2: C, 69.83; H, 5.86; N, 7.40. Found: C, 69.62; H, 5.63; N, 7.51.
3.1.2. General procedure for the synthesis of 3-acetyl-4-methoxy-1-benzyl-1H-indoles 5a–i
Using the synthetic procedure previously reported by us [
17,
18], 3-acetyl-4-methoxy-1
H-indole (189 mg, 1 mmol) was dissolved in DMF (1 mL) at 0 °C and dry sodium hydride (120 mg, 5 mmol) was added. After stirring for 2 min, the appropriate benzyl bromide (1.5 mmol) was added dropwise. The resulting solution was placed in a cylindrical quartz tube (diam. 2 cm), stirred and irradiated in a microwave oven at 100 W and at continuous temperature (50 °C) for 5 min. A saturated NaHCO
3 solution was added. The reaction mixture was extracted with ethyl acetate (10 mL × 3) and dried over Na
2SO
4. After removal of the solvent under reduced pressure, the crude mixture was purified by flash chromatography using a mixture of cyclohexane/ethylacetate (6:4).
3-Acetyl-1-(2-methylbenzyl)-4-methoxy-1H-indole (5a). Yield: 64%; mp: 138–140 °C. 1H-NMR (CDCl3): δ = 2.29 (s, 3H, CH3), 2.66 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 5.24 (s, 2H, CH2), 6.61 (d, 1H, J = 7.9, ArH), 6.83 (d, 1H, J = 7.4, ArH), 6.95 (d, 1H, J = 8.2, ArH), 7.12–7.25 (m, 3H, ArH), 7.56 ppm (s, 1H, ArH); Anal. calcd for C19H19NO2: C 77.79, H 6.53, N 4.77, found: C 77.83, H 6.49, N 4.73.
3-Acetyl-1-(3-methylbenzyl)-4-methoxy-1H-indole (5b). Yield: 73%; mp: 117–119 °C. 1H-NMR (CDCl3): δ = 2.31 (s, 3H, CH3), 2.70 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 5.26 (s, 2H, CH2), 6.70 (d, J = 7.9, 1H, ArH), 6.93–6.96 (m, 3H, ArH), 7.12–7.25 (m, 3H, ArH), 7.73 ppm (s, 1H, ArH); Anal. calcd for C19H19NO2: C 77.79, H 6.53, N 4.77, found: C 77.62, H 6.38, N 4.62.
3-Acetyl-1-(4-methylbenzyl)-4-methoxy-1H-indole (5c). Yield: 61%; mp: 100–102 °C. 1H-NMR (CDCl3): δ = 2.31 (s, 3H, CH3), 2.67 (s, 3H, CH3), 3.97 (s, 3H, OCH3), 5.25 (s, 2H, CH2), 6.68 (d, J = 7.7, 1H, ArH), 6.95–7.20 (m, 6H, ArH), 7.71 ppm (s, 1H, ArH); Anal. calcd for C19H19NO2: C 77.79, H 6.53, N 4.77, found: 77.56, H 6.39, N 4.93.
3-Acetyl-1-(2,3-dimethylbenzyl)-4-methoxy-1H-indole (5d). Yield: 99%; mp: 145–147 °C. 1H-NMR (CDCl3): δ = 2.16 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.66 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 5.25 (s, 2H, CH2), 6.70–6.74 (m, 2H, ArH), 6.96–7.14 (m, 2H, ArH), 7.17–7.26 (m, 2H, ArH), 7.52 (s, 1H, ArH); Anal. calcd for C20H21NO2: C 78.15, H 6.89, N 4.56, found: C 78.23, H 6.71, N 4.38.
3-Acetyl-1-(2,4-dimethylbenzyl)-4-methoxy-1H-indole (5e). Yield: 60%; mp: 114–116 °C. 1H-NMR (CDCl3): δ = 2.23 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.66 (s, 3H, CH3), 3.99 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 6.71 (d, J = 7.9, 1H, ArH), 6.78 (d, J = 7.9, 1H, ArH), 6.94–6.98 (m, 2H, ArH), 7.05 (s, 1H, ArH), 7.18–7.26 (m, 1H, ArH), 7.54 (s, 1H, ArH); Anal. calcd for C20H21NO2: C 78.15, H 6.89, N 4.56, found: C 78.41, H 6.72, N 4.71.
3-Acetyl-1-(2,5-dimethylbenzyl)-4-methoxy-1H-indole (5f). Yield: 63%; mp: 130–132 °C. 1H-NMR (CDCl3): δ = 2.23 (s, 6H, CH3), 2.67 (s, 3H, CH3), 3.99 (s, 3H, OCH3), 5.19 (s, 2H, CH2), 6.71–6.73 (m, 2H, ArH), 6.98–7.21 (m, 4H, ArH), 7.54 (s, 1H, ArH); Anal. calcd for C20H21NO2: C 78.15, H 6.89, N 4.56, found: C 78.39, H 7.01, N 4.21.
3-Acetyl-1-(2,6-dimethylbenzyl)-4-methoxy-1H-indole (5g). Yield: 78%; mp: 140–142 °C. 1H-NMR (CDCl3): δ = 2.24 (s, 6H, CH3), 2.60 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 6.75 (d, J = 7.7, 1H, ArH), 7.12–7.32 (m, 6H, ArH); Anal. calcd for C20H21NO2: C 78.15, H 6.89, N 4.56, found: C 78.46, H 6.69, N 4.68.
3-Acetyl-1-(3,5-dimethylbenzyl)-4-methoxy-1H-indole (5h). Yield: 73%; mp: 110–112 °C. 1H-NMR (CDCl3): δ = 2.26 (s, 6H, CH3), 2.69 (s, 3H, CH3), 3.98 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 6.69 (d, J = 7.9, 1H, ArH), 6.77 (s, 1H, ArH), 6.93–6.97 (m, 2H, ArH), 7.19 (t, J = 7.97, 1H, ArH), 7.72 (s, 1H, ArH); Anal. calcd for C20H21NO2: C 78.15, H 6.89, N 4.56, found: C 78.23, H 6.71, N 4.38.
3-Acetyl-1-(4-fluoro-3,5-dimethylbenzyl)-4-methoxy-1H-indole (5i). Yield: 61%; mp: 128–130 °C. 1H-NMR (CDCl3): δ = 2.20 (s, 6H, CH3), 2.69 (s, 3H, CH3), 3.97 (s, 3H, OCH3), 5.16 (s, 2H, CH2), 6.69 (d, J =7.9, 1H, ArH), 6.80 (d, J = 6.6, 2H, ArH), 6.93 (d, J = 8.2, 1H, ArH), 7.16–7.21 (m, 1H, ArH), 7.69 (s, 1H, ArH); Anal. calcd for C20H20FNO2: C 73.83, H 6.20, N 4.30, found: C 73.43, H 6.24, N 4.46.
3.1.3. General procedure for the synthesis of 4-[1-benzyl-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoates 6a–i
Adopting the synthetic procedure previously reported by us [
17,
18,
20], a mixture of 3-acetyl-4-methoxy-1-benzyl-1
H-indole (1 mmol), diethyl oxalate (219 mg, 1.5 mmol) and a catalytic amount of NaOCH
3 was suspended in anhydrous THF (2 mL). The reaction mixture was placed in a cylindrical quartz tube (diam. 2 cm), stirred and irradiated at continuous temperature in a microwave oven for two successive time intervals under the same conditions (250 Watt, 2 min, 50 °C). The solvent was concentrated under reduced pressure and collected yellow solid was crystallized from ethanol and diethyl ether (1:4).
4-[1-(2-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6a). Yield: 96%; mp: 167 °C dec. 1H-NMR (DMSO-d6): δ = 1.22 (t, J = 7.1, 3H, CH3), 2.24 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 4.09 (q, J = 7.1, 2H, CH2), 5.36 (s, 2H, CH2), 6.59–7.44 (m, 9H ArH and CH); Anal. calcd for C23H23NO5: C 70.21, H 5.89, N 3.56, found C 70.32, H 5.76, N 3.69.
4-[1-(3-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6b). Yield: 98%; mp: 151–153 °C. 1H-NMR (DMSO-d6): δ = 1.22 (t, J = 7.1, 3H, CH3), 2.23 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 4.09 (q, J = 7.1, 2H, CH2), 5.32 (s, 2H, CH2), 6.54–7.64 (m, 9H, ArH and CH); Anal. calcd for C23H23NO5: C 70.21, H 5.89, N 3.56, found C 70.39, H 5.96, N 3.41.
4-[1-(4-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6c). Yield: 99%; mp: 198 °C dec. 1H-NMR (DMSO-d6): δ = 1.22 (t, J = 7.1, 3H, CH3), 2.23 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 4.12 (q, J = 7.1, 2H, CH2), 5.32 (s, 2H, CH2), 6.55–7.64 (m, 9H, ArH and CH); Anal. calcd for C23H23NO5: C 70.21, H 5.89, N 3.56, found C 70.09, H 6.02, N 3.41.
4-[1-(2,3-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6d). Yield: 97%; mp: 172–174 °C. 1H-NMR (DMSO-d6): δ = 1.23 (t, J = 7.1, 3H, CH3), 2.11 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 4.10 (q, J = 7.1, 2H, CH2) 5.36 (s, 2H, CH2), 6.53–7.40 (m, 8H, ArH and CH); Anal. calcd for C24H25NO5: C 70.75, H 6.18, N 3.44, found C 70.71, H 6.22, N 3.40.
4-[1-(2,4-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6e). Yield: 98%; mp: 200–202 °C. 1H-NMR (DMSO-d6): δ = 1.25 (t, J = 7.1, 3H, CH3), 2.17 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 4.10 (q, J = 7.1, 2H, CH2), 5.31 (s, 2H, CH2), 6.62–7.43 (m, 8H, ArH and CH); Anal. calcd for C24H25NO5: C 70.75, H 6.18, N 3.44, found C 70.58, H 6.34, N 3.28.
4-[1-(2,5-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6f). Yield: 94%, mp: 180–182 °C. 1H-NMR (DMSO-d6): δ = 1.23 (t, J = 7.1, 3H, CH3), 2.15 (s, 6H, CH3), 3.85 (s, 3H, OCH3), 4.10 (q, J = 7.1, 2H, CH2), 5.30 (s, 2H, CH2), 6.64–7.41 (m, 8H, ArH and CH); Anal. calcd for C24H25NO5: C 70.75, H 6.18, N 3.44, found C 70.61, H 6.13, N 3.38.
4-[1-(2,6-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6g). Yield: 91%, mp: 195–197 °C. 1H-NMR (DMSO-d6): δ = 1.18 (t, J = 7.1, 3H, CH3), 1.91 (s, 6H, CH3), 3.57 (s, 3H, OCH3), 4.02 (q, J = 6.8, 2H, CH2), 5.30 (s, 2H, CH2), 6.62–7.25 (m, 8H, ArH and CH); Anal. calcd for C24H25NO5: C 70.75, H 6.18, N 3.44, found C 70.82, H 6.27, N 3.31.
4-[1-(3,5-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6h). Yield: 96%, mp: 270 °C dec. 1H-NMR (DMSO-d6): δ = 1.23 (t, J = 7.1, 3H, CH3), 2.18 (s, 6H, CH3), 3.82 (s, 3H, OCH3), 4.12 (q, J = 7.1, 2H, CH2), 5.28 (s, 2H, CH2), 6.58–7.65 (m, 8H, ArH and CH); Anal. calcd for C24H25NO5:C 70.75, H 6.18, N 3.44, found C 70.82, H 6.09, N 3.51.
4-[1-(4-Fluoro-3,5-dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (6i). Yield: 98%, mp 255–257 °C. 1H-NMR (DMSO-d6): δ = 1.22 (t, J = 7.1, 3H, CH3), 2.13 (s, 6H, CH3), 3.82 (s, 3H, OCH3), 4.09 (q, J = 7.1, 2H, CH2), 5.27 (s, 2H, CH2), 6.60–7.65 (m, 7H, ArH and CH); Anal. calcd for C24H24FNO5: C 67.75, H 5.69, N 3.29, found C 67.79, H 5.29, N 3.25.
3.1.4. General procedure for the synthesis of 4-[1-benzyl-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids 7a–i
Following the synthetic procedure previously reported by us [
17,
18,
20], the appropriate 4-[1-benzyl-4-methoxy-1
H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoate (1 mmol) was dissolved in methanol (5 mL) and treated with 2 N NaOH (5 mL, 50 mmol). The reaction mixture was stirred at room temperature for 1.5 h and then acidified with conc. HCl to give the corresponding hydrolyzed derivative. The desired products were crystallized from a mixture of ethanol and diethyl ether (1:4).
4-[1-(2-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7a). Yield: 60%, mp 164–166 °C. 1H-NMR (DMSO-d6): δ = 2.30 (s, 3H, CH3), 3.92 (s, 3H, OCH3), 5.51 (s, 2H, CH2), 6.60–7.60 (m, 8H, ArH a\][0-9a-z]nd CH), 8.26 (s, 1H, ArH), 13.7 (bs, 1H, OH), 15.7 (bs, 1H, OH); 13C-NMR ([D6]DMSO): δ = 21.8, 56.2, 56.6, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 125.7, 128.7, 134.8, 136.8, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C21H19NO5: C 69.03, H 5.24, N 3.83, found C 69.07, H 5.28, N 3.87.
4-[1-(3-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7b). Yield: 45%, mp 150–152 °C. 1H-NMR (DMSO-d6): δ = 2.24 (s, 3H, CH3), 3.89 (s, 3H, OCH3), 5.46 (s, 2H, CH2), 6.78–7.58 (m, 8H, ArH and CH), 8.50 (s, 1H, ArH); 13C-NMR ([D6]DMSO): δ = 24.6, 56.2, 59.4, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 126.0, 128.6, 130.9, 134.8, 136.1, 137.5, 138.3, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C21H19NO5: C 69.03, H 5.24, N 3.83, found C 69.11, H 5.17, N 3.94.
4-[1-(4-Methylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7c). Yield: 58%, mp 141–143 °C. 1H-NMR (DMSO-d6): δ = 2.24 (s, 3H, CH3), 3.89 (s, 3H, OCH3), 5.44 (s, 2H, CH2), 6.77–7.56 (m, 8H, ArH and CH), 8.48 (s, 1H, ArH); 13C-NMR ([D6]DMSO): δ = 24.3, 56.2, 59.1, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 128.9, 133.2, 134.8, 135.4, 137.5, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C21H19NO5: C 69.03, H 5.24, N 3.83, found C 68.97, H 5.11, N 3.73.
4-[1-(2,3-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7d). Yield: 66%, mp 160–162 °C. 1H-NMR (DMSO-d6): δ = 2.18 (s, 3H, CH3), 2.26 (s, 3H, CH3), 3.91 (s, 3H, OCH3), 5.52 (s, 2H, CH2), 6.46–7.61 (m, 7H, ArH and CH), 8.20 (s, 1H, ArH); 13C-NMR ([D6]DMSO): δ = 19.3, 22.1, 56.2, 56.9, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 125.6, 125.9, 134.8, 135.8, 136.7, 137.3, 137.5, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H21NO5: C 69.65, H 5.58, N 3.69, found C 69.69, H 5.54, N 3.65.
4-[1-(2,4-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7e). Yield: 60%, mp 143–145 °C. 1H-NMR (DMSO-d6): δ = 2.22 (s, 3H, CH3), 2.23 (s, 3H, CH3), 3.89 (s, 3H, OCH3), 5.42 (s, 2H, CH2), 6.58–7.93 (m, 7H, ArH e CH), 8.14 (s, 1H, ArH); 13C-NMR ([D6]DMSO): δ = 22.1, 24.6, 56.2, 56.6, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 125.9, 128.8, 130.8, 134.4, 134.8, 135.3, 136.7, 137.5, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H21NO5: C 69.65, H 5.58, N 3.69, found C 69.71, H 5.43, N 3.51.
4-[1-(2,5-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7f). Yield: 59%, mp 163–165 °C. 1H-NMR (DMSO-d6): δ = 2.13 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.93 (s, 3H, OCH3), 5.46 (s, 2H, CH2), 6.56–7.63 (m, 7H, ArH e CH), 8.23 ppm (s, 1H, ArH); 13C-NMR (DMSO-d6): δ = 21.8, 24.6, 56.2, 56.6, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 125.9, 128.8, 130.8, 133.8, 134.8, 135.3, 137.3, 137.5, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H21NO5: C 69.65, H 5.58, N 3.69, found C 69.82, H 5.41, N 3.78.
4-[1-(2,6-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7g). Yield: 76%, mp 173–175 °C. 1H-NMR (DMSO-d6): δ = 2.19 (s, 6H, CH3), 3.92 (s, 3H, OCH3), 5.40 (s, 2H, CH2), 6.85–7.44 (m, 7H, ArH e CH), 7.63 ppm (s, 1H, ArH); 13C-NMR (DMSO-d6): δ = 22.1, 54.1, 56.2, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 125.6, 125.9, 134.8, 136.7, 137.5, 141.1, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H21NO5: C 69.65, H 5.58, N 3.69, found C 69.49, H 5.72, N 3.48.
4-[1-(3,5-Dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7h). Yield: 52%; mp: 120–122 °C. 1H-NMR (DMSO-d6): δ = 2.19 (s, 6H, CH3), 3.89 (s, 3H, OCH3), 5.41 (s, 2H, CH2), 6.78–7.59 (m, 7H, 6ArH and CH), 8.48 ppm (s, 1H, ArH); 13C-NMR DMSO-d6): δ = 24.1, 56.2, 59.7, 103.4, 111.1, 111.7, 113.9, 121.1, 125.2, 127.9, 134.8, 136.0, 137.5, 138.2, 152.1, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H21NO5: C 69.65, H 5.58, N 3.69, found: C 69.45, H 5. 41, N 3.75.
4-[1-(4-Fluoro-3,5-dimethylbenzyl)-4-methoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (7i). Yield: 40%; mp: 153–155 °C. 1H-NMR (DMSO-d6): δ = 2.15 (s, 6H, CH3), 3.89 (s, 3H, OCH3), 5.39 (s, 2H, CH2), 6.78–7.21 (m, 5H, ArH e CH), 7.57 (s, 1H, ArH), 8.47 ppm (s, 1H, ArH); 13C-NMR ([D6]DMSO): δ = 18.1, 56.2, 59.7, 103.4, 111.1, 111.7, 113.9, 121.1, 123.7, 125.2, 129.5, 131.6, 134.8, 137.5, 152.1, 160.5, 164.5, 187.6, 189.7 ppm; Anal. calcd for C22H20FNO5: C 66.49, H 5.07, N 3.52, found: C 66.36, H 5.28, N 3.39.